|
2,4-Dimethylphenol
CASRN 105-67-9
Contents
0466
2,4-Dimethylphenol; CASRN 105-67-9
Health assessment information on a chemical substance is included in IRIS only
after a comprehensive review of chronic toxicity data by U.S. EPA health
scientists from several Program Offices and the Office of Research and
Development. The summaries presented in Sections I and II represent a
consensus reached in the review process. Background information and
explanations of the methods used to derive the values given in IRIS are
provided in the Background Documents.
STATUS OF DATA FOR 2,4-Dimethylphenol
File On-Line 11/01/1990
Category (section) Status Last Revised
----------------------------------------- -------- ------------
Oral RfD Assessment (I.A.) on-line 11/01/1990
Inhalation RfC Assessment (I.B.) no data
Carcinogenicity Assessment (II.) no data
_I. CHRONIC HEALTH HAZARD ASSESSMENTS FOR NONCARCINOGENIC EFFECTS
__I.A. REFERENCE DOSE FOR CHRONIC ORAL EXPOSURE (RfD)
Substance Name -- 2,4-Dimethylphenol
CASRN -- 105-67-9
Last Revised -- 11/01/1990
The oral Reference Dose (RfD) is based on the assumption that thresholds exist
for certain toxic effects such as cellular necrosis. It is expressed in units
of mg/kg-day. In general, the RfD is an estimate (with uncertainty spanning
perhaps an order of magnitude) of a daily exposure to the human population
(including sensitive subgroups) that is likely to be without an appreciable
risk of deleterious effects during a lifetime. Please refer to the Background
Document for an elaboration of these concepts. RfDs can also be derived for
the noncarcinogenic health effects of substances that are also carcinogens.
Therefore, it is essential to refer to other sources of information concerning
the carcinogenicity of this substance. If the U.S. EPA has evaluated this
substance for potential human carcinogenicity, a summary of that evaluation
will be contained in Section II of this file.
___I.A.1. ORAL RfD SUMMARY
Critical Effect Experimental Doses* UF MF RfD
-------------------- ----------------------- ----- --- ----------
Clinical signs NOAEL: 50 mg/kg/day 3000 1 2E-2
(lethargy, prostra- mg/kg/day
tion, and ataxia) LOAEL: 250 mg/kg/day
and hematological
changes
Mouse Subchronic
Oral Gavage
U.S. EPA, 1989
*Conversion Factors: None
___I.A.2. PRINCIPAL AND SUPPORTING STUDIES (ORAL RfD)
U.S. EPA. 1989. Ninety-day gavage study in Albino mice using 2,4-
dimethylphenol. Study No. 410-2831, prepared by Dynamac Corporation,
Rockville, MD, for the Office of Solid Waste and Emergency Response,
Washington, DC.
2,4-Dimethylphenol was administered daily to male and female albino mice by
gavage. The animals (30/sex/group) were dosed for 90 days with 5.0, 50.0, or
250 mg 2,4-dimethylphenol/kg/day. Two control groups, untreated and vehicle
(corn oil), of similar size were also established. Effects examined included
mortality, clinical signs, body weights, food consumption, opthalmology,
hematology and clinical chemistry, organ weights, and gross histopathology.
Although 15 deaths occurred during this study (mostly because of errors in
technical procedure), only one was considered as possibly treatment-related:
a male in the 5 mg/kg/day-dose group died during the first 30 days of the
experiment. No significant differences were found between treated and vehicle
control groups in mean body weight, body weight gains, food consumption, or
eye examinations at any dosage. Toxicologically relevant clinical signs
observed only after week 6 in the high-dose groups of both genders included:
squinting, lethargy, prostration, and ataxia, with onset shortly after dosing.
Statistically significant hematological changes (p<0.05) included lower mean
corpuscular volume and mean corpuscular hemoglobin concentration in females at
terminal, but not interim, sacrifice.
At interim sacrifice in female mid- and high-dose groups, blood urea nitrogen
(BUN) levels were significantly below vehicle controls; whereas at final
sacrifice in the female mid-dose group, BUN levels were significantly higher
than vehicle controls. Low-dose males at interim sacrifice had significantly
higher cholesterol levels. Significant differences were not found in gross
necropsy or histopathological evaluations, or in organ weights, except for an
increase in adrenal weights of low-dose females. The LOAEL and NOAEL for this
study were 250 and 50 mg/kg/day, respectively.
___I.A.3. UNCERTAINTY AND MODIFYING FACTORS (ORAL RfD)
UF -- An uncertainty factor of 3000 was established: 10 each for inter- and
intraspecies variability and 30 for lack of chronic toxicity data, data in a
second species and reproductive/developmental studies.
MF -- None
___I.A.4. ADDITIONAL COMMENTS (ORAL RfD)
A 14-day gavage study with 2,4-dimethylphenol conducted by the same laboratory
that conducted the principal study, revealed lethargy, prostration, and ataxia
in males and females in the 250 mg/kg/day-dose group, the same dose at which
effects were found in the principal study (U.S. EPA, 1987).
No other long-term toxicity, reproductive, or developmental studies of 2,4-
dimethylphenol were found in the data bases SEARCHed. Literature concerning
2,6-dimethylphenol was identified, but an SAR-based RfD is considered
inappropriate when a valid long-term toxicity study for 2,4-dimethylphenol is
available.
___I.A.5. CONFIDENCE IN THE ORAL RfD
Study -- Medium
Data Base -- Low
RfD -- Low
Confidence in the study is medium, since it examined appropriate endpoints and
identified both a LOAEL and a NOAEL. The results of this study are consistent
with those of a 14-day gavage study. The data base provides no information on
chronic and reproductive studies. Low confidence in both the data base and
oral RfD follows.
___I.A.6. EPA DOCUMENTATION AND REVIEW OF THE ORAL RfD
Source Document -- This assessment is not presented in any existing U.S. EPA
document.
Other EPA Documentation -- None
Agency Work Group Review -- 02/21/1990
Verification Date -- 02/21/1990
___I.A.7. EPA CONTACTS (ORAL RfD)
Please contact the Risk Information Hotline for all questions concerning this
assessment or IRIS, in general, at (513)569-7254 (phone), (513)569-7159 (FAX)
or RIH.IRIS@EPAMAIL.EPA.GOV (internet address).
__I.B. REFERENCE CONCENTRATION FOR CHRONIC INHALATION EXPOSURE (RfC)
Substance Name -- 2,4-Dimethylphenol
CASRN -- 105-67-9
Not available at this time.
_II. CARCINOGENICITY ASSESSMENT FOR LIFETIME EXPOSURE
Substance Name -- 2,4-Dimethylphenol
CASRN -- 105-67-9
This substance/agent has not undergone a complete evaluation and determination
under US EPA's IRIS program for evidence of human carcinogenic potential.
_VI. BIBLIOGRAPHY
Substance Name -- 2,4-Dimethylphenol
CASRN -- 105-67-9
Last Revised -- 11/01/1990
__VI.A. ORAL RfD REFERENCES
U.S. EPA. 1987. Fourteen-day gavage study in Albino mice using 2,4-
dimethylphenol. Study No. 410-2830, prepared by Dynamac Corporation,
Rockville, MD for the Office of Solid Waste and Emergency Response,
Washington, DC.
U.S. EPA. 1989. Ninety-day gavage study in Albino mice using 2,4-
dimethylphenol. Study No. 410-2831, prepared by Dynamac Corporation,
Rockville, MD, for the Office of Solid Waste and Emergency Response,
Washington, DC.
__VI.B. INHALATION RfC REFERENCES
None
__VI.C. CARCINOGENICITY ASSESSMENT REFERENCES
None
_VII. REVISION HISTORY
Substance Name -- 2,4-Dimethylphenol
CASRN -- 105-67-9
-------- -------- --------------------------------------------------------
Date Section Description
-------- -------- --------------------------------------------------------
11/01/1990 I.A. Oral RfD summary on-line
11/01/1990 VI. Bibliography on-line
01/01/1992 IV. Regulatory Action section on-line
VIII. SYNONYMS
Substance Name -- 2,4-Dimethylphenol
CASRN -- 105-67-9
Last Revised -- 11/01/1990
105-67-9
Phenol, 2,4-dimethyl-
Caswell No. 907A
EPA Pesticide Chemical Code 086804
HSDB 4253
m-XYLENOL
NSC 3829
RCRA WASTE NUMBER U101
1-HYDROXY-2,4-DIMETHYLBENZENE
2,4-dimethylphenol
2,4-Xylenol
4-HYDROXY-1,3-DIMETHYLBENZENE
4,6-DIMETHYLPHENOL
Last updated: 5 May 1998
URL: http://www.epa.gov/iris/SUBST/0466.HTM
|
